To some, malaria drug is worse than risking disease

Published 4:00 am, Sunday, May 17, 1998

Noe Valley resident Jennifer Patterson says she got as far as Malaysia on her round-the-world trip before she went crazy.

Kristin Loudis, who lives in the Richmond District, believes she lost her mind swimming in the Niger River in the West African nation of Mali.

Physician Sunita Jayakar of Mountain View says she returned from India to face a year of insomnia, vomiting and numbness in her limbs and head.

All three had taken Lariam, the widely prescribed malaria drug whose manufacturer, Hoffmann-La Roche of Switzerland, is the target of federal lawsuits recently filed in San Jose, Minneapolis and Newark, N.J. All allege the manufacturer failed to warn users of the frequency, severity and duration of side effects. The company has denied the charges.

In a debate raging on both sides of the Atlantic, the benefits of the controversial drug are being weighed against the potentially deadly effects of malaria.

A growing chorus of critics - most of them former users of Lariam, the brand name of mefloquine hydrochloride - say the drug's neuropsychiatric side effects are so bizarre and so poorly understood that it is better to risk contracting malaria, a parasitic blood-borne disease spread by mosquitoes.

Loudis, Patterson and Jayakar recovered. Others haven't.

On April 22, a British coroner reported that the suicide of London barrister Francis Mcleod Matthews - after months of anguish following a trip to East Africa - "more likely than not" had been caused, in part, by Lariam.

In 1995, a 23-year-old Philadelphia man had a panic attack after his third Lariam dose and jumped from a second-story hotel room window in Nairobi, Kenya. He is now a paraplegic.

"The international scientific community is concerned about the safety of this drug. Americans need to be made aware," said Berkeley lawyer Susan Rose, who is involved in each of the federal suits against Hoffmann-La Roche. Similar litigation is pending in England.

Lariam's defenders - including most doctors and researchers, backed by the federal Centers for Disease Control and Prevention, the federal Food and Drug Administration and the World Health Organization, claim adverse neuropsychiatric effects of all kinds occur among less than one percent of users.

"This drug may not be entirely ideal," said Paul Goldberger, director of the FDA's Division of Special Pathogens. "It nevertheless represents an important agent, particularly with the emergence of drug-resistant malaria."

University of Toronto researcher Jay Keystone said data showed that between 1 in 10,000 and 1 in 13,000 users had seizures or psychotic reactions. But as many as 1 in 200, he said, experience "intermediate or moderate events" - reactions including insomnia, anxiety, dizziness and nightmares.

"The bottom line is mefloquine is preventing a fatal disease," Keystone said. "If 93 or 95 percent of the people who take the drug tolerate it with no problems or minor problems, we have to keep this thing in perspective."

Kristin Loudis said: "Since I've come back three years ago, my brain hasn't worked the way it used to. It's as if someone has gone in and rearranged the furniture. The drug is worse than the malaria."

Jennifer Patterson added: "Malaria's treatable; this isn't. If I go to a hospital and say I'm having side effects, they'll put me in a mental hospital."

Why Lariam is a critical drug&lt;

By conservative estimate, malaria strikes an estimated 200 million people and kills 1 million worldwide each year, nearly all in tropical regions. As global tourism increases, more Westerners with no immunity from repeated exposures risk falling ill.

Americans, who haven't experienced endemic malaria since the 1950s, may be especially at risk, according to Philip J. Rosenthal, a UCSF-San Francisco General Hospital researcher.

Of the four types of malaria parasite, just one - falciparum - can be lethal. It is this bug, however, that developed resistance to anti-malaria drugs such as chloroquine beginning in the 1950s.

Lariam, consequently, has been very important both as for preventing and treating falciparum since first sold in the United States in 1989. Nearly 300,000 Lariam prescriptions were written in the United States last year, according to IMS HEALTH, a Pennsylvania health information company that collects data for the FDA.

Richard Thompson, the Sunnyvale specialist who prescribed Lariam for Sunita Jayakar, said he had prescribed it hundreds of times and gotten a report of adverse side effects from only one other patient.

"Dr. Jayakar wouldn't take it again, and I don't blame her," Thompson said. "But her experience is very rare."

Hoffmann-La Roche issues a detailed warning with each prescription, saying the drug must be discontinued if mental symptoms appear because they may be precursors to more serious psychiatric events. Prospective users with underlying psychiatric conditions, it adds, may be especially vulnerable to "emotional disturbances."

Two FDA advisory committees looked at Lariam when it was first marketed. Both focused more on dosage levels than on side effects.

"There were concerns about the neuropsychiatric effects," FDA drug expert Phil Coyne said, but the committees assured themselves that Hoffman-La Roche had fulfilled its disclosure requirements. If problems remained, the panels concluded, they stemmed from physicians' failures to draw patients' attention to the side effects.

Stephen Fried, author of "Bitter Pills: Inside the Hazardous World of Legal Drugs," holds the drug lobby and the FDA indirectly responsible for adverse reactions. Companies don't spend enough time or money monitoring drugs after they are approved, he says. But Fried also believes doctors ignore the known effects of Lariam and other legal drugs.

"They're terrible about reporting reactions," Fried said. "They don't want to get involved or be the subjects of lawsuits."

Madness in Malaysia&lt;

In September 1995, Patterson and her Wellesley College roommate Kirsten Leute traveled through New Zealand, Australia, Indonesia, Singapore and Malaysia before disaster struck.

Patterson, 24 at the time, took three Lariam pills over three weeks. After the second pill, she lay awake at night in a small town near Kuala Lumpur, hallucinating.

Days later, she found herself wandering aimlessly through a large city, Penang, alternatively feeling agitated or, at worst, paranoid. Then, she fell ill with diarrhea and began to have hot flashes.

One night, she paced the bathroom of a youth hostel until dawn, then presented herself at a hospital emergency room and begged for Valium, a tranquilizer. She was allowed only aspirin.

After returning to her hotel, she took out her pocket knife and gazed at her wrists - but stopped short of inflicting further harm on herself. She fled to the airport, where she boarded a plane for Singapore. A day later, she returned home.

"It took me about a year and a half to get my life back in order," Patterson said.

"There's a dark side'&lt;

Leute experienced no ill effects, but stopped taking the drug when a German physician she met days after Patterson departed told her it was controversial in Europe.

During the third week of a tour of West Africa in 1994, Loudis had violent dreams.

"In one, I was parachuting out of an airplane with an Uzi machine gun and killing my friends and family. In another, I was chased down a dirt road by men in tanks,and I ran into a compound where dogs attacked me.

"I had them every few nights. You wake up and think, "Omigod, there's a dark side.' It became a joke with my friends. They were having similar dreams, and they'd say, "I had another mefloquine dream last night!' "

Swimming in a river in Mali, the nightmares became daytime hallucinations: "I had this panic attack and thought all my friends would drown me. When they got close, I'd hang on to the boat and say, "Get away! Get away!' "

In Mali and Ghana, Loudis also began to experience feverish sweats and respiratory problems. One night, she made the mistake of drinking whisky, which Australian researchers say may precipitate "psychoneurological events" when mixed with mefloquine. When she awoke, her fever had skyrocketed, and she felt delirious.

The morning of her 33rd birthday, she lay in a hut in a Ghanaian village, feeling near death; a nurse helped break her fever. After a week's recuperation, Loudis found her way to an airport, where she boarded a plane to London for a connecting flight to San Francisco.

"I still have problems," she said. "I'd like people to know these are your risks. I was one of the unfortunate ones."

Just before her 12th trip to Bombay in 17 years, Jayakar, the Mountain View physician, read a pro-Lariam piece in the Journal of the American Medical Association, and took the drug for the first time.

After the fifth tablet, she fell ill. As a physician, she availed herself of everything potentially relevant in medical detection's repertoire, including lab tests, a brain scan, abdominal ultrasound and a spinal tap. Nothing showed up.

"While I was doing this, my internist read about Lariam. He said, "This is a drug reaction,' " recalled Jayakar, 36 when she got sick.

The symptoms lasted more than a year. By the time she was well, Jayakar was 20 pounds lighter, weighing 88 pounds.

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"Doctors don't know what's going on - or they think it's psychosomatic," she said. "If I wasn't a physician myself, I probably would have felt the same.

"It was unbelievable. I would rather have been exposed to malaria than take this medication." &lt;

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